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Identification
Name Rivastigmine
Accession Number DB00989 (APRD00321)
Type small molecule
Groups approved
Description

Rivastigmine is a parasympathomimetic or cholinergic agent for the treatment of mild to moderate dementia of the Alzheimer’s type. Rivastigmine is a cholinesterase inhibitor that inhibits both butyrylcholinesterase and acetylcholinesterase.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Ena 713 Free Base
Salts Not Available
Brand names
Name Company
Exelon
Exelon Patch
Brand mixtures Not Available
Categories
  • Parasympathomimetics
  • Neuroprotective Agents
  • Cholinesterase Inhibitors
  • Nootropic Agents
  • Cholinergic Agents
CAS number 123441-03-2
Weight Average: 250.3367
Monoisotopic: 250.168127958
Chemical Formula C14H22N2O2
InChI Key InChIKey=XSVMFMHYUFZWBK-NSHDSACASA-N
InChI
InChI=1S/C14H22N2O2/c1-6-16(5)14(17)18-13-9-7-8-12(10-13)11(2)15(3)4/h7-11H,6H2,1-5H3/t11-/m0/s1
Plain Text
IUPAC Name
3-[(1S)-1-(dimethylamino)ethyl]phenyl N-ethyl-N-methylcarbamate
SMILES
CCN(C)C(=O)OC1=CC=CC(=C1)[C@H](C)N(C)C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Carbamates and Derivatives
  • Phenols and Derivatives
  • Anisoles
  • Phenyl Esters
Substructures
  • Carbamates and Derivatives
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Aromatic compounds
  • Anisoles
  • Phenyl Esters
Pharmacology
Indication For the treatment of mild to moderate dementia associated with Parkinson's disease or of the Alzheimer's type.
Pharmacodynamics Rivastigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. An early pathophysiological feature of Alzheimer's disease that is associated with memory loss and cognitive deficits is a deficiency of acetylcholine as a result of selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus. Tacrine is postulated to exert its therapeutic effect by enhancing cholinergic function. While the precise mechanism of rivastigmine's action is unknown, it is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. If this proposed mechanism is correct, rivastigmine's effect may lessen as the disease progresses and fewer cholinergic neurons remain functionally intact.
Mechanism of action Rivastigmine is a carbamate derivative that is structurally related to physostigmine, but not to donepezil and tacrine. The precise mechanism of rivastigmine has not been fully determined, but it is suggested that rivastigmine binds reversibly with and inactivates chlolinesterase (eg. acetylcholinesterase, butyrylcholinesterase), preventing the hydrolysis of acetycholine, and thus leading to an increased concentration of acetylcholine at cholinergic synapses. The anticholinesterase activity of rivastigmine is relatively specific for brain acetylcholinesterase and butyrylcholinesterase compared with those in peripheral tissues.
Absorption Not Available
Volume of distribution
  • 1.8 to 2.7 L/kg
Protein binding 40%
Metabolism
Rivastigmine is rapidly metabolized by cholinesterase-mediated hydrolysis.
Route of elimination Rivastigmine is extensively metabolized primarily via cholinesterase-mediated hydrolysis to the decarbamylated metabolite NAP226-90. Renal excretion of the metabolites is the major route of elimination. Less than 1% of the administered dose is excreted in the feces.
Half life 1.5 hours
Clearance
  • renal cl=2.1-2.8 L/hr
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
  • Dr reddys laboratories inc
  • Sun pharmaceutical industries ltd
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Solution Oral
Prices
Unit description Cost Unit
Exelon 30 4.6 mg/24hr Patches Box 252.18 USD box
Exelon 30 9.5 mg/24hr Patches Box 252.18 USD box
Exelon 4.6 mg/24hr patch 8.08 USD patch
Exelon 9.5 mg/24hr patch 8.08 USD patch
Exelon 1.5 mg capsule 4.81 USD capsule
Exelon 3 mg capsule 4.81 USD capsule
Exelon 4.5 mg capsule 4.81 USD capsule
Exelon 6 mg capsule 4.81 USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6316023 1999-01-08 2019-01-08
United States 4948807 1992-08-14 2012-08-14
Canada 2315784 2006-06-27 2019-01-08
Properties
State solid
Experimental Properties
Property Value Source
logP 2.3 Not Available
Predicted Properties
Property Value Source
water solubility 2.04e+00 g/l ALOGPS
logP 2.45 ALOGPS
logP 2.41 ChemAxon
logS -2.1 ALOGPS
pKa (strongest basic) 8.89 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 32.78 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 73.37 ChemAxon
polarizability 28.53 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Camps P, Munoz-Torrero D: Cholinergic drugs in pharmacotherapy of Alzheimer’s disease. Mini Rev Med Chem. 2002 Feb;2(1):11-25. Pubmed
  2. Rosler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, Stahelin HB, Hartman R, Gharabawi M: Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: international randomised controlled trial. BMJ. 1999 Mar 6;318(7184):633-8. Pubmed
  3. Finkel SI: Effects of rivastigmine on behavioral and psychological symptoms of dementia in Alzheimer’s disease. Clin Ther. 2004 Jul;26(7):980-90. Pubmed
  4. Rosler M, Retz W, Retz-Junginger P, Dennler HJ: Effects of two-year treatment with the cholinesterase inhibitor rivastigmine on behavioural symptoms in Alzheimer’s disease. Behav Neurol. 1998;11(4):211-216. Pubmed
  5. Emre M, Aarsland D, Albanese A, Byrne EJ, Deuschl G, De Deyn PP, Durif F, Kulisevsky J, van Laar T, Lees A, Poewe W, Robillard A, Rosa MM, Wolters E, Quarg P, Tekin S, Lane R: Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med. 2004 Dec 9;351(24):2509-18. Pubmed
  6. Birks J, Grimley Evans J, Iakovidou V, Tsolaki M, Holt FE: Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD001191. Pubmed# Naik RS, Hartmann J, Kiewert C, Duysen EG, Lockridge O, Klein J: Effects of rivastigmine and donepezil on brain acetylcholine levels in acetylcholinesterase-deficient mice. J Pharm Pharm Sci. 2009;12(1):79-85. Pubmed
  7. Farlow MR: Update on rivastigmine. Neurologist. 2003 Sep;9(5):230-4. Pubmed
External Links
Resource Link
KEGG Drug D03822 Link_out
KEGG Compound C11766 Link_out
PubChem Compound 77991 Link_out
PubChem Substance 46507452 Link_out
ChemSpider 70377 Link_out
BindingDB 10620 Link_out
Therapeutic Targets Database DAP000149 Link_out
PharmGKB PA451262 Link_out
Drug Product Database 2242118 Link_out
RxList http://www.rxlist.com/cgi/generic2/rivastig.htm Link_out
Drugs.com http://www.drugs.com/cdi/rivastigmine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Rivastigmine Link_out
ATC Codes
  • N06DA03
AHFS Codes
  • 12:04.00
PDB Entries
FDA label show (74 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Amantadine Possible antagonism of action
Amitriptyline Possible antagonism of action
Amoxapine Possible antagonism of action
Azatadine Possible antagonism of action
Benzatropine Possible antagonism of action
Biperiden Possible antagonism of action
Brompheniramine Possible antagonism of action
Chlorpheniramine Possible antagonism of action
Chlorpromazine Possible antagonism of action
Chlorprothixene Possible antagonism of action
Cimetidine Possible antagonism of action
Clemastine Possible antagonism of action
Clomipramine Possible antagonism of action
Clozapine Possible antagonism of action
Cyclizine Possible antagonism of action
Cyclobenzaprine Possible antagonism of action
Cyproheptadine Possible antagonism of action
Darifenacin Possible antagonism of action
Desipramine Possible antagonism of action
Dicyclomine Possible antagonism of action
Dimenhydrinate Possible antagonism of action
Diphenhydramine Possible antagonism of action
Disopyramide Possible antagonism of action
Doxepin Possible antagonism of action
Flavoxate Possible antagonism of action
Flupenthixol Possible antagonism of action
Glutethimide Possible antagonism of action
Glycopyrrolate Possible antagonism of action
Hydroxyzine Possible antagonism of action
Hyoscyamine Possible antagonism of action
Imipramine Possible antagonism of action
Isocarboxazid Possible antagonism of action
Loxapine Possible antagonism of action
Maprotiline Possible antagonism of action
Meclizine Possible antagonism of action
Meperidine Possible antagonism of action
Mesoridazine Possible antagonism of action
Methotrimeprazine Possible antagonism of action
Mirtazapine Possible antagonism of action
Moclobemide Possible antagonism of action
Nortriptyline Possible antagonism of action
Olanzapine Possible antagonism of action
Orphenadrine Possible antagonism of action
Oxybutynin Possible antagonism of action
Perphenazine Possible antagonism of action
Phenelzine Possible antagonism of action
Pimozide Possible antagonism of action
Procainamide Possible antagonism of action
Prochlorperazine Possible antagonism of action
Promethazine Possible antagonism of action
Propericiazine Possible antagonism of action
Quetiapine Possible antagonism of action
Quinidine Possible antagonism of action
Thioproperazine Possible antagonism of action
Thioridazine Possible antagonism of action
Tizanidine Possible antagonism of action
Trazodone Possible antagonism of action
Trifluoperazine Possible antagonism of action
Trihexyphenidyl Possible antagonism of action
Trimethobenzamide The therapeutic effects of the anticholinergic, Trimethobenzamide, and/or the acetylcholinesterase inhibitor (central), Rivastigmine, may be reduced due to antagonism. Monitor therapeutic effects of both agents.
Trospium The therapeutic effects of the anticholinergic, Trospium, and/or the acetylcholinesterase inhibitor (central), Rivastigmine, may be reduced due to antagonism. Monitor therapeutic effects of both agents.
Food Interactions Not Available
Targets

1. Acetylcholinesterase

Pharmacological action: yes
Actions: inhibitor

Rapidly hydrolyzes choline released into the synapse

Organism class: human
UniProt ID: P22303 Link_out
Gene: ACHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kennedy JS, Polinsky RJ, Johnson B, Loosen P, Enz A, Laplanche R, Schmidt D, Mancione LC, Parris WC, Ebert MH: Preferential cerebrospinal fluid acetylcholinesterase inhibition by rivastigmine in humans. J Clin Psychopharmacol. 1999 Dec;19(6):513-21. Pubmed
  2. Goldblum D, Garweg JG, Bohnke M: Topical rivastigmine, a selective acetylcholinesterase inhibitor, lowers intraocular pressure in rabbits. J Ocul Pharmacol Ther. 2000 Feb;16(1):29-35. Pubmed
  3. Grossberg GT, Stahelin HB, Messina JC, Anand R, Veach J: Lack of adverse pharmacodynamic drug interactions with rivastigmine and twenty-two classes of medications. Int J Geriatr Psychiatry. 2000 Mar;15(3):242-7. Pubmed
  4. Stahl SM: The new cholinesterase inhibitors for Alzheimer’s disease, Part 1: their similarities are different. J Clin Psychiatry. 2000 Oct;61(10):710-1. Pubmed
  5. Gottwald MD, Rozanski RI: Rivastigmine, a brain-region selective acetylcholinesterase inhibitor for treating Alzheimer’s disease: review and current status. Expert Opin Investig Drugs. 1999 Oct;8(10):1673-1682. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Birks J, Grimley Evans J, Iakovidou V, Tsolaki M, Holt FE: Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD001191. Pubmed# Naik RS, Hartmann J, Kiewert C, Duysen EG, Lockridge O, Klein J: Effects of rivastigmine and donepezil on brain acetylcholine levels in acetylcholinesterase-deficient mice. J Pharm Pharm Sci. 2009;12(1):79-85. Pubmed
  8. Lalli S, Albanese A: Rivastigmine in Parkinson’s disease dementia. Expert Rev Neurother. 2008 Aug;8(8):1181-8. Pubmed
  9. Onor ML, Trevisiol M, Aguglia E: Rivastigmine in the treatment of Alzheimer’s disease: an update. Clin Interv Aging. 2007;2(1):17-32. Pubmed
  10. Farlow MR: Update on rivastigmine. Neurologist. 2003 Sep;9(5):230-4. Pubmed
  11. Greig NH, Lahiri DK, Sambamurti K: Butyrylcholinesterase: an important new target in Alzheimer’s disease therapy. Int Psychogeriatr. 2002;14 Suppl 1:77-91. Pubmed

2. Cholinesterase

Pharmacological action: yes
Actions: inhibitor

An acylcholine + H(2)O = choline + a carboxylate

Organism class: human
UniProt ID: P06276 Link_out
Gene: BCHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Stahl SM: The new cholinesterase inhibitors for Alzheimer’s disease, Part 1: their similarities are different. J Clin Psychiatry. 2000 Oct;61(10):710-1. Pubmed
  3. Gottwald MD, Rozanski RI: Rivastigmine, a brain-region selective acetylcholinesterase inhibitor for treating Alzheimer’s disease: review and current status. Expert Opin Investig Drugs. 1999 Oct;8(10):1673-1682. Pubmed
  4. Birks J, Grimley Evans J, Iakovidou V, Tsolaki M, Holt FE: Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD001191. Pubmed# Birks J: Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593. Pubmed# Naik RS, Hartmann J, Kiewert C, Duysen EG, Lockridge O, Klein J: Effects of rivastigmine and donepezil on brain acetylcholine levels in acetylcholinesterase-deficient mice. J Pharm Pharm Sci. 2009;12(1):79-85. Pubmed
  5. Smith DA: Treatment of Alzheimer’s disease in the long-term-care setting. Am J Health Syst Pharm. 2009 May 15;66(10):899-907. Pubmed
  6. Bassil N, Grossberg GT: Novel regimens and delivery systems in the pharmacological treatment of Alzheimer’s disease. CNS Drugs. 2009;23(4):293-307. Pubmed# Lalli S, Albanese A: Rivastigmine in Parkinson’s disease dement
    ia. Expert Rev Neurother. 2008 Aug;8(8):1181-8. Pubmed
  7. Onor ML, Trevisiol M, Aguglia E: Rivastigmine in the treatment of Alzheimer’s disease: an update. Clin Interv Aging. 2007;2(1):17-32. Pubmed
  8. Farlow MR: Update on rivastigmine. Neurologist. 2003 Sep;9(5):230-4. Pubmed
  9. Greig NH, Lahiri DK, Sambamurti K: Butyrylcholinesterase: an important new target in Alzheimer’s disease therapy. Int Psychogeriatr. 2002;14 Suppl 1:77-91. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19